Approximately 40% of pharmaceutical compounds have poor aqueous solubility, which is a major limiting factor for a new drug to successfully pass through clinical trials (Lipinski (2002), Am Pharm Rev 5:82-85). Numerous approaches have been used to solubilize hydrophobic drugs for improving their delivery to patients. Several examples of such approaches include milling, complexing with cyclodextrins, forming salts, and using surfactants or polymeric micelles. Each of these approaches has certain advantages and disadvantages so improved approaches to solubilizing drugs are eagerly sought.
Polymeric micelles are self-assembled amphiphilic block or graft copolymers. Polymeric micelles have attracted attention as promising colloidal drug delivery systems (Torchilin, J Controlled Release 2001, 73, 137; Allen et al., Colloids and Surfaces B: Biointerfaces 1999, 16, 3; and Otsuka et al., Current Opinion in Colloid & Interface Science 2001, 6, 3). In these colloidal systems, the hydrophobic block typically forms the core, essentially forming a “microcontainer” for a lipophilic cargo molecules (Kataoka et al., Adv. Drug Delivery Rev. 2001, 47, 113). The hydrophilic portion of the micelle forms the outer shell, stabilizing the interface between the core and the external aqueous environment.
Compared to surfactant-based micellar systems, polymer-based micelles can display apparent advantages such as lower critical micelle concentration (CMC) and reduced toxicity. Despite these advantages, the use of known micellar systems is somewhat limited due to unsuitable biodegradability, biocompatibility, encapsulation efficiency, stability, clinical side effects of the formulations, and the difficulty and cost associated with preparation of known micellar formulations. Accordingly, there is a need for additional micellar systems that possess some of the known advantages associated with micellar drug delivery systems, but that have increased biocompatibility and are easier and less expensive to prepare.